Abstract
Different delivery mechanisms have been proposed in the literature for targeted therapies in the treatment of lymphedema. They vary from simple and direct injection to sophisticated induction of gene expression in a targeted tissue. We conducted a systematic review of publications assessing the use of viral vectors for gene transfer in lymphedema treatment. We hypothesized that viral vectors are an effective way to deliver targeted therapy in lymphedema treatment. We conducted a comprehensive systematic review of the published literature on targeted therapies associated with lymphedema surgery using the PubMed database. Eligibility criteria excluded papers that reported use of viral vectors for other medical conditions. s, presentations, reviews, meta-analyses, and non-English language articles were also excluded. From 21 potential articles found in the literature, fourteen fulfilled study eligibility criteria. Positive outcomes in terms of lymphangiogenesis were seen. The viral vectors used included adenovirus and recombinant adeno-associated virus. Most of the genes expressed were growth factors, but expression of dominant-negative transforming growth factor-β1 receptor-II or Prox1 was also proposed. Five studies targeted genetic expression on lymphedema tissue, five on transplanted lymph nodes, two on skeletal muscle, and one on adipose-derived stem cells. Publications assessing use of viral vectors for gene transfer in lymphedema treatment demonstrated that it is an effective mechanism of delivering targeted therapies. However, to date, all studies were experimental and further studies must be performed before translating these therapies into clinical practice.
Highlights
BackgroundLymphedema is a chronic lymphatic condition that affects 140 to 200 million people in the world [1, 2]
We conducted a systematic review of publications assessing the use of viral vectors for gene transfer in lymphedema treatment
Publications assessing use of viral vectors for gene transfer in lymphedema treatment demonstrated that it is an effective mechanism of delivering targeted therapies
Summary
Lymphedema is a chronic lymphatic condition that affects 140 to 200 million people in the world [1, 2]. The majority of patients develop clinical manifestation only months after the lymphatic lesion, causing tissue fibrosis and demonstrating the relevance of further inflammatory steps [3,4,5]. Development of targeted therapies has attracted the interest of investigators around the world. Those therapies have been proposed in two main groups: targeted therapies modulating inflammation, such as those that control Th2-inflammatory responses [6,7,8], and targeted therapies inducing lymphangiogenesis, such as vascular endothelial growth factor (VEGF) C or adipose-derived stem cells (ADSCs) [9,10,11]. Translation of some of these therapies into clinical practice raises concerns for increased risk of metastasis in oncologic patients [10]
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